An interdisciplinary approach will be used for identification and characterization of the forms of bioactive human growth hormone in human blood and at target tissue. Somatic cell fusion and immunological methods will be used to create a library of monoclonal hybridomas which secrete antibodies directed specifically to the various pituitary hGH isohormones and fragments. The monospecific antibodies will be employed as biochemical tools for the quantitation and isolation of the circulating hormone, which will then be chemically characterized. Lactogenic and somatogenic activities will be measured with two sensitive and specific in vitro bioassays using rat lymphoma cells and human fibroblasts. These systems will be extended for use in radioreceptor assays. The monoclonal antibodies, binding assays, and bioassays will be collectively employed to study structure/function relationships among the GH isohormones and the processing of hormone by target tissue. This may establish specific physiological roles for GH isohormones and help to determine whether enzymatic modification of growth hormone reflects an endocrine control mechanism in which processing leads to new or altered bioactivities compared to the parent hormone.